Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model

Samuel Mon-Wei Yu; John Yongjoon Choi; Jamie Kady; Marina De Cos; Jenny S. Wong; Emily King; Nour Younis; Nadim Al Rahy; Soltan Al Chaar; Houda Djebli; Siawosh Eskandari; Stephen Samuel; Tamara Merhej; Nivedha Sukumar; Jia Ren Lin; Jia Yun Chen; Yilin Xu; Sandro Santagata; Astrid Weins; Melissa Yeung; Paolo Cravedi; Kirk N. Campbell; Dario Lemos; Joseph V. Bonventre; Michael A. Brehm; Jamil Azzi

doi:10.1016/j.kint.2025.02.027

Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model

Samuel Mon-Wei Yu
, John Yongjoon Choi
, Jamie Kady
, Marina De Cos
, Jenny S. Wong
, Emily King
, Nour Younis
, Nadim Al Rahy
, Soltan Al Chaar
, Houda Djebli
, Siawosh Eskandari
, Stephen Samuel
, Tamara Merhej
, Nivedha Sukumar
, Jia Ren Lin
, Jia Yun Chen
, Yilin Xu
, Sandro Santagata
, Astrid Weins
, Melissa Yeung

Paolo Cravedi, Kirk N. Campbell, Dario Lemos, Joseph V. Bonventre, Michael A. Brehm, Jamil Azzi

Research output: Contribution to journal › Article › peer-review

Abstract

Human kidney organoids derived from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) have become novel tools for studying various kidney pathologies. Here, we transplanted ESC-derived kidney organoids into humanized mice with a mature human adaptive immune system developed through thymic education. As judged by histology and immunophenotyping, the transplanted HLA-mismatched kidney organoids trigged a robust alloimmune response, characterized by a dense immune cell infiltrate and enhanced memory T cell phenotype in the allograft 30 days post-transplantation. Multiplexed immunofluorescence revealed expression of functional markers of various immune cell infiltrates in response to organoid allografts, mimicking the T cell-mediated rejection process in humans. This validated our model as a novel platform to study various therapeutic strategies to control alloimmunity. Splenocytes isolated from organoid-transplanted hosts showed an alloantigen-specific memory response against 2D kidney organoids ex vivo. Overall, our study indicates that transplanting kidney organoids in humanized mice may be a valuable tool for studying human allogeneic immunity.

Original language	English
Pages (from-to)	1011-1016
Number of pages	6
Journal	Kidney International
Volume	107
Issue number	6
DOIs	https://doi.org/10.1016/j.kint.2025.02.027
State	Published - Jun 2025

Keywords

human kidney organoids
humanized mice model
kidney transplantation

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10.1016/j.kint.2025.02.027

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Mon-Wei Yu, S., Choi, J. Y., Kady, J., De Cos, M., Wong, J. S., King, E., Younis, N., Al Rahy, N., Al Chaar, S., Djebli, H., Eskandari, S., Samuel, S., Merhej, T., Sukumar, N., Lin, J. R., Chen, J. Y., Xu, Y., Santagata, S., Weins, A., ... Azzi, J. (2025). Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model. Kidney International, 107(6), 1011-1016. https://doi.org/10.1016/j.kint.2025.02.027

@article{8a92e3e0a1da4b29b63b0ce0d3b937e9,

title = "Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model",

abstract = "Human kidney organoids derived from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) have become novel tools for studying various kidney pathologies. Here, we transplanted ESC-derived kidney organoids into humanized mice with a mature human adaptive immune system developed through thymic education. As judged by histology and immunophenotyping, the transplanted HLA-mismatched kidney organoids trigged a robust alloimmune response, characterized by a dense immune cell infiltrate and enhanced memory T cell phenotype in the allograft 30 days post-transplantation. Multiplexed immunofluorescence revealed expression of functional markers of various immune cell infiltrates in response to organoid allografts, mimicking the T cell-mediated rejection process in humans. This validated our model as a novel platform to study various therapeutic strategies to control alloimmunity. Splenocytes isolated from organoid-transplanted hosts showed an alloantigen-specific memory response against 2D kidney organoids ex vivo. Overall, our study indicates that transplanting kidney organoids in humanized mice may be a valuable tool for studying human allogeneic immunity.",

keywords = "human kidney organoids, humanized mice model, kidney transplantation",

author = "\{Mon-Wei Yu\}, Samuel and Choi, \{John Yongjoon\} and Jamie Kady and \{De Cos\}, Marina and Wong, \{Jenny S.\} and Emily King and Nour Younis and \{Al Rahy\}, Nadim and \{Al Chaar\}, Soltan and Houda Djebli and Siawosh Eskandari and Stephen Samuel and Tamara Merhej and Nivedha Sukumar and Lin, \{Jia Ren\} and Chen, \{Jia Yun\} and Yilin Xu and Sandro Santagata and Astrid Weins and Melissa Yeung and Paolo Cravedi and Campbell, \{Kirk N.\} and Dario Lemos and Bonventre, \{Joseph V.\} and Brehm, \{Michael A.\} and Jamil Azzi",

note = "Publisher Copyright: {\textcopyright} 2025 International Society of Nephrology",

year = "2025",

month = jun,

doi = "10.1016/j.kint.2025.02.027",

language = "English",

volume = "107",

pages = "1011--1016",

journal = "Kidney International",

issn = "0085-2538",

publisher = "Elsevier B.V.",

number = "6",

}

Mon-Wei Yu, S, Choi, JY, Kady, J, De Cos, M, Wong, JS, King, E, Younis, N, Al Rahy, N, Al Chaar, S, Djebli, H, Eskandari, S, Samuel, S, Merhej, T, Sukumar, N, Lin, JR, Chen, JY, Xu, Y, Santagata, S, Weins, A, Yeung, M, Cravedi, P, Campbell, KN, Lemos, D, Bonventre, JV, Brehm, MA & Azzi, J 2025, 'Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model', Kidney International, vol. 107, no. 6, pp. 1011-1016. https://doi.org/10.1016/j.kint.2025.02.027

TY - JOUR

T1 - Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model

AU - Mon-Wei Yu, Samuel

AU - Choi, John Yongjoon

AU - Kady, Jamie

AU - De Cos, Marina

AU - Wong, Jenny S.

AU - King, Emily

AU - Younis, Nour

AU - Al Rahy, Nadim

AU - Al Chaar, Soltan

AU - Djebli, Houda

AU - Eskandari, Siawosh

AU - Samuel, Stephen

AU - Merhej, Tamara

AU - Sukumar, Nivedha

AU - Lin, Jia Ren

AU - Chen, Jia Yun

AU - Xu, Yilin

AU - Santagata, Sandro

AU - Weins, Astrid

AU - Yeung, Melissa

AU - Cravedi, Paolo

AU - Campbell, Kirk N.

AU - Lemos, Dario

AU - Bonventre, Joseph V.

AU - Brehm, Michael A.

AU - Azzi, Jamil

PY - 2025/6

Y1 - 2025/6

N2 - Human kidney organoids derived from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) have become novel tools for studying various kidney pathologies. Here, we transplanted ESC-derived kidney organoids into humanized mice with a mature human adaptive immune system developed through thymic education. As judged by histology and immunophenotyping, the transplanted HLA-mismatched kidney organoids trigged a robust alloimmune response, characterized by a dense immune cell infiltrate and enhanced memory T cell phenotype in the allograft 30 days post-transplantation. Multiplexed immunofluorescence revealed expression of functional markers of various immune cell infiltrates in response to organoid allografts, mimicking the T cell-mediated rejection process in humans. This validated our model as a novel platform to study various therapeutic strategies to control alloimmunity. Splenocytes isolated from organoid-transplanted hosts showed an alloantigen-specific memory response against 2D kidney organoids ex vivo. Overall, our study indicates that transplanting kidney organoids in humanized mice may be a valuable tool for studying human allogeneic immunity.

AB - Human kidney organoids derived from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) have become novel tools for studying various kidney pathologies. Here, we transplanted ESC-derived kidney organoids into humanized mice with a mature human adaptive immune system developed through thymic education. As judged by histology and immunophenotyping, the transplanted HLA-mismatched kidney organoids trigged a robust alloimmune response, characterized by a dense immune cell infiltrate and enhanced memory T cell phenotype in the allograft 30 days post-transplantation. Multiplexed immunofluorescence revealed expression of functional markers of various immune cell infiltrates in response to organoid allografts, mimicking the T cell-mediated rejection process in humans. This validated our model as a novel platform to study various therapeutic strategies to control alloimmunity. Splenocytes isolated from organoid-transplanted hosts showed an alloantigen-specific memory response against 2D kidney organoids ex vivo. Overall, our study indicates that transplanting kidney organoids in humanized mice may be a valuable tool for studying human allogeneic immunity.

KW - human kidney organoids

KW - humanized mice model

KW - kidney transplantation

UR - https://www.scopus.com/pages/publications/105004736221

U2 - 10.1016/j.kint.2025.02.027

DO - 10.1016/j.kint.2025.02.027

M3 - Article

C2 - 40127865

AN - SCOPUS:105004736221

SN - 0085-2538

VL - 107

SP - 1011

EP - 1016

JO - Kidney International

JF - Kidney International

IS - 6

ER -

Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model

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